Abstract Major health disparities continue to impact tribal nations, yet a serious shortage of scientists conducting American Indian (AI) health disparities research persists. For several years, Cherokee Nation, the University of Oklahoma (OU) system, and the Oklahoma Medical Research Foundation (OMRF) have partnered to address this issue by building tribal research capacity through the Native American Research Centers for Health (NARCH) mechanism. In this cycle of NARCH funding, the partnership among Cherokee Nation, OU, and OMRF continues and, importantly for student career enhancement, expands to include the Oklahoma State University (OSU) system as a key partner for student career enhancement activities. The overall mission of Cherokee NARCH is to develop durable research capacity within the context of an American Indian (AI) tribal nation to address health disparities. To achieve this goal, the five Specific Aims of Cherokee NARCH are: 1. to strengthen administrative infrastructure, including a Leadership Team (LT) and a Tribal-Campus Advisory Committee (TCAC), that ensures integration of career enhancement, capacity building, and research activities; 2. to educate the next generation of researchers to engage meaningfully with Cherokee Nation in the context of tribal research, focusing on undergraduate, graduate and health professions students; 3. to build tribal capacity by developing a set of research codes to govern the conduct of genomic and other biomedical research predicated on the concept of tribal data sovereignty; 4. to conduct innovative research and pilot research capable of seeding future research projects performed by researchers seeking to work within the Cherokee Nation setting; and 5. to evaluate activities of the partnership, including monitoring progress of student career enhancement, capacity building, and research/pilot research projects, and evaluation of the overall Cherokee NARCH program. Cherokee NARCH provides a crucial opportunity to solidify the foundation for tribal capacity in health disparities research. The addition of OSU strengthens Cherokee NARCH by its remarkable success in the education of AI students in scientific and health professions fields, including the advent of the first tribally affiliated medical school in the US. Cherokee NARCH therefore provides an unprecedented environment in which a tribe, two research-intensive universities with large AI student populations (OU and OSU), and a biomedical research foundation (OMRF) will work synergistically to reduce the unacceptable disparities in health that continue to affect AI people. /